Long intergenic non-protein coding RNA 1273 confers sorafenib resistance in hepatocellular carcinoma via regulation of methyltransferase 3

Bioengineered, Journal Year: 2022, Volume and Issue: 13(2), P. 3108 - 3121

Published: Jan. 17, 2022

Hepatocellular carcinoma (HCC) is often diagnosed in patients with advanced disease who are ineligible for curative surgical therapies. Sorafenib a first-line agent approved the treatment of HCC. However, frequent resistance HCC cells to sorafenib greatly reduces its efficacy. Herein, we describe novel long non-coding RNA (lncRNA) conferring resistance. Long intergenic non-protein coding 1273 (LINC01273) was significantly overexpressed human and sorafenib-resistant tissues, linking it poor overall relapse-free survival. We established Huh7 (Huh7-SR) SMMC-7721 (SMMC-7721-SR) cells, found that knockdown LINC01273 repressed viability, colony formation, DNA synthesis rate Huh7-SR SMMC-7721-SR cells. The level N6-methyladenosine (m6A) decreased, which rescued by silencing. Mechanistically, complementarity bound miR-600, served as 'reservoir' increasing miR-600 stability, facilitating targeting methyltransferase 3 (METTL3), m6A 'writer', resulting reducing METTL3 level. In addition, modified m6A, increased modification, followed decay presence YTHDF2, 'reader'. Our findings reveal key role newly identified LINC01273/miR-600/METTL3 feedback regulatory axis may be promising effective intervention

Language: Английский

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LncRNAs and CircRNAs in cancer

MedComm, Journal Year: 2022, Volume and Issue: 3(2)

Published: May 12, 2022

Abstract It is well known that noncoding RNAs (ncRNAs) cannot encode proteins, but they can play important regulatory roles in tumors by combining with RNAs, and DNAs. As more studies reveal the underlying mechanisms of long (lncRNAs) circular (circRNAs) cancer, their huge application potential cancer therapy be ignored. For example, lncRNAs involved tumor‐related signal transduction pathways, cell cycle control, DNA damage, epigenetic regulation, microRNA control. A group confirmed abnormal expression affect progression. Furthermore, as covalently closed continuous ncRNAs, many recent have shown circRNAs effects other biological significances cancer. Interestingly, were found to translational functions. This has greatly attracted people's attention research. In this review, we introduce some representative cancers, respectively. focus on functions clinical therapeutic implications lnRNAs neuroblastoma. Our review also focuses providing rationale relevant references for novel biomarkers neuroblastoma diagnosis, prognosis, treatment.

Language: Английский

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High expression of small nucleolar RNA host gene 3 predicts poor prognosis and promotes bone metastasis in prostate cancer by activating transforming growth factor-beta signaling

Bioengineered, Journal Year: 2022, Volume and Issue: 13(1), P. 1895 - 1907

Published: Jan. 1, 2022

Bone metastasis is closely related to tumor death in prostate cancer (PC). Long noncoding RNA small nucleolar host gene 3 (SNHG3) has been implicated the initiation and progression of multiple human cancers. Nevertheless, biological function SNHG3 PC not elucidated. Our results indicated that was upregulated bone metastasis-positive tissues compared metastasis-negative adjacent normal tissues. High expression indicates advanced clinicopathological features predicts poor prognosis patients with PC. Meanwhile, knockdown suppressed proliferation, migration, invasion abilities cells inhibited cell bone. Mechanistically, enhanced transforming growth factor beta receptor 1 (TGFBR1) activated factor-Beta (TGF-β) signaling by targeting miR-214-3p. study demonstrated novel role SNHG3/miR-214-3p/TGF-β axis PC, indicating may act as a biomarker promising therapeutic target against

Language: Английский

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IGF2BP2 Drives Cell Cycle Progression in Triple‐Negative Breast Cancer by Recruiting EIF4A1 to Promote the m6A‐Modified CDK6 Translation Initiation Process

Advanced Science, Journal Year: 2023, Volume and Issue: 11(1)

Published: Nov. 20, 2023

Abstract IGF2BP2 is a new identified N6‐methyladenosine (m6A) reader and associated with poor prognosis in many tumors. However, its role related mechanism breast cancer, especially triple‐negative cancer (TNBC), remains unclear. In this study, it found that highly expressed TNBC due to the lower methylation level promoter region. Functional mechanical studies displayed could promote proliferation G1/S phase transition of cell cycle via directly regulating CDK6 an m6A‐dependent manner. Surprising, regulation protein levels by changes translation rate during initiation, rather than mRNA stability. Moreover, EIF4A1 be recruited output CDK6, providing evidence for regulatory between m6A translation. Downregulation enhance sensitivity abemaciclib, CDK4/6 inhibitor. To sum up, our study revealed facilitate recruiting also provided potential therapeutic target diagnosis treatment TNBC, as well strategy broadening drug indications inhibitors.

Language: Английский

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Novel insights into the multifaceted roles of m6A-modified LncRNAs in cancers: biological functions and therapeutic applications

Biomarker Research, Journal Year: 2023, Volume and Issue: 11(1)

Published: April 17, 2023

Abstract N6-methyladenosine (m 6 A) is considered as the most common and important internal transcript modification in several diseases like type 2 diabetes, schizophrenia especially cancer. As a main target of m A methylation, long non-coding RNAs (lncRNAs) have been proved to regulate cellular processes at various levels, including epigenetic modification, transcriptional, post-transcriptional, translational post-translational regulation. Recently, accumulating evidence suggests that A-modified lncRNAs greatly participate tumorigenesis cancers. In this review, we systematically summarized biogenesis identified A-lncRNAs variety cancers, well their potential diagnostic therapeutic applications biomarkers targets, hoping shed light on novel strategies for cancer treatment.

Language: Английский

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